Abstract/Summary Core A: Islet Production Core. Islet function and integrity represent a critical node in glucose homeostasis. The Islet Production Core supports research by DRC investigators who analyze the functional responses to genetic or pharmacologic interventions in islets isolated from pancreases of mice and humans. The UCSF DRC also has a very strong islet immunology and transplantation program. Isolated islets are essential for studies oriented towards counteracting islet autoimmunity and minimizing transplant rejection. Purpose: The DRC Islet Production Core consolidates, enhances and disseminates expertise and resources in islet preparation to DRC investigators who currently study or have plans to study pancreatic islet cell biology, islet function and/or transplantation. The Core provides the following capabilities: 1. Islet Purification. Processing and preparation of human and mouse islets for use in islet biology, autoimmunity and transplantation studies. 2. Islet Functional Analysis. Real time biological and biochemical analysis of insulin production and other functional aspects of human and mouse islets to characterize islet activity under different conditions and to assess islet preparation quality for transplantation studies. Benefits to DRC Community: DRC investigators need not commit time and resources to establishing this highly specialized capability within their laboratory. The uniform islet preparation methods used by different DRC investigators also can enable cross-study comparisons to generate unanticipated linkages between studies. 35 different projects totaling $6,580,009 annual direct costs currently are benefiting from this Core. In the past 2 years alone, mouse islets were prepared a total of 807 times (from 1 to 20 mice per prep) for 12 DRC research laboratories. A further 45 mouse islet preparations were conducted for 3 other investigators as they considered whether their studies had applications to diabetes research. UCSF also has a leading clinical islet transplantation program. The facilities developed for those human islet transplants have been leveraged by the DRC for making human islets available for research studies. In the last year, human research islets were prepared for studies by six DRC investigators. With the capacity of the facilities and the availability of human research-grade pancreases, we propose to provide this unique human islets capability to investigators beyond UCSF (see Regional Core). Technology Development: Unique capabilities in human and model organisms facilitate translational research by Core users at UCSF and throughout the region. The DRC also has robust programs, funded through the DRC grant, that have successfully developed improvements in the monitoring of islet preparation and function. This enables the activities of the Core to benefit not only translational and basic research, but also clinical trials and the patients participating in them.